Cancer biologists are currently exploring the role that in vivo imaging may play in studying small animal models of cancer. Imaging technologies can be used to visualize and measure morphology, physiology, metabolism, as well as specific molecular targets and processes. The non-invasive nature of imaging permits multiple studies within a single experimental subject and also provides a natural bridge into the clinical environment. Positron Emission Tomography (PET) is one of the imaging modalities under consideration, and in recent years, our group, and others, have developed high-resolution small animal PET scanners for this purpose. Several of these small animal PET systems are now being used in cancer applications including basic studies of tumor biology, new probes for tumor detection and in vivo monitoring of therapeutic effect. MicroPET II is a second generation small animal PET scanner designed to achieve 1 mm (1 pL) spatial resolution in vivo with a sensitivity of - 2%. This compares with 1.8 mm (8 pL) resolution and 0.5% sensitivity in the initial prototype microPET. In this proposal, a rigorous evaluation of this new instrument will performed, and data corrections implemented to ensure that accurate quantification is achieved in vivo. Three important issues in small animal PET imaging also will be addressed: i) How reproducible are in vivo microPET measurements? ii) What are the limits of detection for microPET imaging? iii) Can the blood input function be obtained non-invasively in the mouse by rapid dynamic imaging? Finally, the high spatial resolution of microPET II will be used to examine the degrading effects of positron range in longer-lived radionuclides that are of interest for molecular imaging (for example 1-1 24, Br-76) but which emit medium to high energy positrons. MicroPET II is designed to be a powerful new tool for cancer researchers. The careful evaluation of this system along with the implementation of quantitative imaging and studies of reproducibility, detection sensitivity and positron range effects, will lay a firm foundation on which to base future studies in mouse models of cancer using microPET II and other similar small animal PET systems.